Longitudinal disease-associated gut microbiome differences in infants with food protein-induced allergic proctocolitis

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

36138438

DOI Digital object identifier for electronic documents.

https://doi.org/10.1186/s40168-022-01322-y

URI

https://pubmed.ncbi.nlm.nih.gov/36138438/

Authors

Martin VM, Virkud YV, Dahan E, Seay HL, Itzkovits D, Vlamakis H, Xavier R, Shreffler WG, Yuan Q, Yassour M

Journal

Microbiome

Year

2022

BACKGROUND: Complex interactions between the gut microbiome and immune cells in infancy are thought to be part of the pathogenesis for the marked rise in pediatric allergic diseases, particularly food allergies. Food protein-induced allergic proctocolitis (FPIAP) is commonly the earliest recognized non-immunoglobulin E (IgE)-mediated food allergy in infancy and is associated with atopic dermatitis and subsequent IgE-mediated food allergy later in childhood. Yet, a large prospective longitudinal study of the microbiome of infants with FPIAP, including samples prior to symptom onset, has not been done. RESULTS: Here, we analyzed 954 longitudinal samples from 160 infants in a nested case-control study (81 who developed FPIAP and 79 matched controls) from 1 week to 1 year of age by 16S rRNA ribosomal gene sequencing as part of the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study. We found key differences in the microbiome of infants with FPIAP, most strongly a higher abundance of a genus of Enterobacteriaceae and a lower abundance of a family of Clostridiales during the symptomatic period. We saw some of these significant taxonomic differences even prior to symptom onset. There were no consistent longitudinal differences in richness or stability diversity metrics between infants with FPIAP and healthy controls. CONCLUSIONS: This study is the first to identify differences in the infant gut microbiome in children who develop FPIAP, some even before they develop symptoms, and provides a foundation for more mechanistic investigation into the pathogenesis of FPIAP and subsequent food allergic diseases in childhood. Video abstract.

Experiment 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/09

Curator: Tolulopeo

Revision editor(s): LGeistlinger, Peace Sandy, Tolulopeo, Fiddyhamma

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Ulcerative proctosigmoiditis chronic ulcerative rectosigmoiditis (disorder),Proctocolitis,proctosigmoiditis,Proctosigmoiditis (disorder),ulcerative (chronic) proctosigmoiditis,ulcerative proctosigmoiditis,Ulcerative proctosigmoiditis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Infants diagnosed without food protein-induced allergic proctocolitis (FPIAP)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP) who had a minimum of 4 longitudinal stool samples in the first year. FPIAP was diagnosed by the treating physician and confirmed by comprehensive study staff chart review.

Group 0 sample size Number of subjects in the control (unexposed) group: 81

Group 1 sample size Number of subjects in the case (exposed) group: 79

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): NIL

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: arcsine square-root

Statistical test: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.20

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Matched on Factors on which subjects have been matched on in a case-control study: age, Matched on: "disease status" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.disease status

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: diet, Confounders controlled for: "symptoms" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.symptoms, Confounders controlled for: "Probiotics use in the first year of life" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Probiotics use in the first year of life, age, mode of birth

Alpha Diversity

Richness Number of species: unchanged

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/10

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy

Source: Fig 3 (A) and 3 (B)

Description: Summary of key differential taxa between infants with FPIAP and healthy controls. A Significantly different taxa comparing infants with FPIAP to healthy controls (q < 0.20; absolute coefficient > = 0.05) when looking at sample subsets: 0–2 months, last pre-symptomatic, first symptomatic, and first resolved. Bars to the right are enriched in infants with FPIAP, while bars to the left are enriched in the controls. Number of samples in each group is shown under the name of the subset analyzed in that model (FPIAP, control). B Significantly different taxa (q < 0.20) when comparing infants with FPIAP to matched controls before their symptom onset (top section) and then during the symptomatic period (lower section) over the first 2 months of age. Association directionality and numbers are as in (A).

Abundance in Group 1: increased abundance in Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP)

NCBI	Quality Control	Links
Blautia
unclassified Eubacteriales

Revision editor(s): Tolulopeo, Peace Sandy

Signature 2

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2024/02/22

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3 (A) and (B)

Description: Summary of key differential taxa between infants with FPIAP and healthy controls. A Significantly different taxa comparing infants with FPIAP to healthy controls (q < 0.20; absolute coefficient > = 0.05) when looking at sample subsets: 0–2 months, last pre-symptomatic, first symptomatic, and first resolved. Bars to the right are enriched in infants with FPIAP, while bars to the left are enriched in the controls. Number of samples in each group is shown under the name of the subset analyzed in that model (FPIAP, control). B Significantly different taxa (q < 0.20) when comparing infants with FPIAP to matched controls before their symptom onset (top section) and then during the symptomatic period (lower section) over the first 2 months of age. Association directionality and numbers are as in (A).

Abundance in Group 1: decreased abundance in Infants diagnosed with food protein-induced allergic proctocolitis (FPIAP)

NCBI	Quality Control	Links
Enterobacteriaceae
Lactobacillus

Revision editor(s): Peace Sandy